This grant supports continuing studies on the regulation of immunity. Most of our present work is concerned with the role of antibody and specific anti-antibody in this process. In our model, antibody is directed against phosphorylcholine (PC). The anti-antibody is directed against the combining region of antibody to phosphorylcholine, and it therefore functions as an anti-receptor antibody or ARA. ARA given passively to adult mice causes suppression of the response to PC which lasts for several weeks or about as long as the antibody persists. In contrast, ARA given to neonates causes unresponsiveness for many months. During the past year we have developed a plaque-forming cell assay (PFC) to demonstrate individual cells producing ARA. The development of the assay is essential for demonstrating this response when animals are also producing anti-PC antibody since anti-PC antibody and ARA neutralize the antibody activities of each other. We have studied the kinetics of the ARA response, the conditions which influence the magnitude of the response, and the cell types required for the response. We have demonstrated that mice immunized repeatedly with PC containing antigens or injected once with a paralyzing dose of a PC containing antigen have ARA-producing cells. The inference is that the autogenously produced ARA is regulating or suppressing the response to PC. During the coming year this grant will support two specific aspects of our overall work: 1) Suppression of tumor growth by ARA, and 2) The primary induction of an ARA response by a mutant strain of R36A which has PC as major determinant in its C-polysaccharide. BIBLIOGRAPHIC REFERENCES: Strayer, D.S., Lee, W.M.F., Rowley, D.A. and Kohler, H. Anti-receptor antibody. II. Induction of Long-Term unresponsiveness in neonatal mice. J. Immunol. 114, 728, 1975; Rowley, D.A., Fitch, F.W., Cosenza, H. and Leserman, L. The 3d cell type required for the antibody response in vitro. In 'Mononuclear Phagocytes in Immunity, Infection and Pathology' Ed. R. van Furth, Blackwell Scientific Publication Ltd., Oxford, Edinburgh, London and Melbourne, 1975.